The question we area seeking to answer is "Why do we have serum albumin?". the most abundant and most familiar of the plasma proteins, albumin has several recognized functions -- fatty acid binding, bilirubin transport, oncotic regulation, nutrition -- and is seen to be remarkably conserved in most vertebrate species. Yet the major purpose of this major protein is not known. The repeating intron-exon pattern of its gene implies that albumin, a multi-domain protein, like its fetal counterpart, Alpha-fetoprotein, evolved from a smaller protein by gene replication. We plan to investigate the evolutionary origins of serum albumin, on the premise that the forerunner of albumin was a smaller molecule resembling a single domain or subdomain of the present structure, and that the function of this smaller molecule will represent the priomordial function of albumin and/or Alpha-fetoprotein. We will first characterize albumins from the lower vertebrate classes as far down the evolutionary scale as an albumin can be identified, currently at about the level of the teleost fish. Then we will search for predecessors, or protoalbumins, in lower chordates and invertebrates. Our experimental approach will apply techniques of protein biochemistry that have been successful in isolating and characterizing native globular fragments of mammalian albumins to isolate and study such proteins from lower animals. Analbuminemia, the total of lack of circulating albumin, has been reported but it is extremely rare. Persons with analbuminemia are not fatally stricken, but have transient edema and chronic hyperlipidemia. An analbuminemic strain of rats has been found to have increased susceptibility to cancer. We propose to establish an Analbuminemia Register to provide long-term surveillance of the state of health and longevity of the analbuminemic humans, in order to identify the physiologic consequences when albumin is chronically absent from the circulations. Our aim is to define the origins and functions of serum albumin so that we may better understand its importance in the circulation in health and be able to administer it wisely in disease.